{"entity":{"id":"cabozantinib","kind":"drug","name":"Cabozantinib","aka":[],"tldr":"A pill that blocks both blood-vessel growth and the MET escape pathway, used in kidney, liver, thyroid and, since 2025, neuroendocrine cancers.","summary":"CELESTIAL: OS 10.2 vs 8.0 months after sorafenib in HCC (HR 0.76). CheckMate 9ER: with nivolumab, first-line RCC. CABINET (2024-25): PFS 13.8 vs 4.4 months in pancreatic NETs and 8.4 vs 3.9 months in extra-pancreatic NETs after prior therapy, leading to FDA approval in March 2025; ESMO 2025 subgroup showed an 81% reduction in progression risk in lung and thymic NETs. COSMIC-312 (with atezolizumab, first-line HCC) improved PFS but not OS.","status":"approved","asOf":"2026-09-07","wikipedia":"https://en.wikipedia.org/wiki/Cabozantinib","links":[{"label":"FDA label (DailyMed)","url":"https://dailymed.nlm.nih.gov/dailymed/search.cfm?query=Cabozantinib"}],"tags":[],"related":[],"indications":["hcc","rcc","neuroendocrine","thyroid"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["cabinet","nct03690388"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":["In kidney cancer: CABOSUN (first line versus sunitinib, PFS benefit), METEOR (second line versus everolimus, OS 21.4 versus 16.5 months), CheckMate 9ER (with nivolumab, OS benefit), COSMIC-313 (triplet, no OS gain) and CONTACT-03 (no benefit from adding atezolizumab). The dose is 40 mg daily with nivolumab, and about 65 percent of patients have a grade 3 or higher event; the long half-life of about 99 hours matters when toxicity appears."],"brand":"Cabometyx","modality":"Small-molecule multi-kinase inhibitor (MET, VEGFR2, AXL, RET)","mechanism":"Oral inhibitor of MET, VEGFR2, AXL, RET, KIT and FLT3; MET/AXL inhibition counters anti-VEGF resistance.","approvals":[{"region":"US","year":2012,"indication":"Medullary thyroid cancer (Cometriq)"},{"region":"US","year":2016,"indication":"Advanced RCC"},{"region":"US","year":2019,"indication":"HCC previously treated with sorafenib"},{"region":"US","year":2025,"indication":"Advanced pancreatic and extra-pancreatic neuroendocrine tumours after prior therapy (CABINET)"},{"region":"US","year":2017,"indication":"First-line advanced RCC (CABOSUN)"},{"region":"US","year":2021,"indication":"First-line advanced RCC with nivolumab (CheckMate 9ER)"},{"region":"EU","year":2014,"indication":"Cometriq for medullary thyroid cancer; 21 Mar 2014. Cabometyx (RCC) Sep 2016"}],"mechanismSteps":["Blocks VEGFR2 on endothelium","Blocks MET and AXL, which tumours upregulate under hypoxia to escape anti-VEGF therapy","Reduces invasion and metastasis signalling"],"dosing":{"route":"Oral","schedule":"60 mg daily (Cabometyx tablets)","modifications":"40 mg then 20 mg for intolerance","monitoring":"Blood pressure, liver enzymes, wound healing"},"toxicity":[{"event":"Hand-foot skin reaction","anyGradePct":46,"grade3PlusPct":17,"note":"CELESTIAL"},{"event":"Hypertension","anyGradePct":29,"grade3PlusPct":16,"note":"CELESTIAL"},{"event":"Diarrhoea","anyGradePct":54,"grade3PlusPct":10,"note":"CELESTIAL"}],"access":[],"regulatoryEvents":[{"date":"2025-03-26","type":"approval","region":"US","note":"NET indication on CABINET","source":"https://www.ncf.net/post/2025-highlights-in-neuroendocrine-cancer"}]},"route":"/drugs/cabozantinib/","neighbours":{"indication":[{"id":"hcc","kind":"indication","name":"Hepatocellular carcinoma","route":"/indications/hcc/"},{"id":"lung-net","kind":"indication","name":"Lung neuroendocrine tumours (typical and atypical carcinoid)","route":"/indications/lung-net/"},{"id":"metastatic-ppgl","kind":"indication","name":"Metastatic pheochromocytoma and paraganglioma","route":"/indications/metastatic-ppgl/"},{"id":"multiple-endocrine-neoplasia","kind":"indication","name":"Multiple endocrine neoplasia syndromes (MEN1, MEN2, MEN4)","route":"/indications/multiple-endocrine-neoplasia/"},{"id":"neuroendocrine","kind":"indication","name":"Neuroendocrine tumours","route":"/indications/neuroendocrine/"},{"id":"osteosarcoma","kind":"indication","name":"Osteosarcoma","route":"/indications/osteosarcoma/"},{"id":"pancreatic-net","kind":"indication","name":"Pancreatic neuroendocrine tumours","route":"/indications/pancreatic-net/"},{"id":"pheochromocytoma-paraganglioma","kind":"indication","name":"Pheochromocytoma and paraganglioma (PPGL)","route":"/indications/pheochromocytoma-paraganglioma/"},{"id":"rcc","kind":"indication","name":"Renal cell carcinoma","route":"/indications/rcc/"},{"id":"small-intestinal-net","kind":"indication","name":"Small intestinal neuroendocrine tumours","route":"/indications/small-intestinal-net/"},{"id":"thyroid","kind":"indication","name":"Thyroid cancer","route":"/indications/thyroid/"}],"trial":[{"id":"nct03690388","kind":"trial","name":"A Study of Cabozantinib Compared With Placebo in Subjects With Radioiodine-refractory Differentiated Thyroid Cancer Who Have Progressed After Prior Va","route":"/trials/nct03690388/"},{"id":"cabinet","kind":"trial","name":"CABINET (Alliance A021602)","route":"/trials/cabinet/"}],"paper":[{"id":"paper-cabinet-cabozantinib-nejm-2024","kind":"paper","name":"CABINET (Alliance A021602): cabozantinib for advanced neuroendocrine tumours","route":"/key-papers/paper-cabinet-cabozantinib-nejm-2024/"}]}}